Extrapolating beyond AACR 2022: The future of MRD testing

Authors: Adam Corner, Ph.D., Market Development Scientist IVD, Bio-Rad Digital Biology Group and Jeremiah McDole, Ph.D., Oncology Segment Manager, Bio-Rad Digital Biology Group

Amidst hundreds of abstracts from this year’s American Association for Cancer Research (AACR) annual meeting in New Orleans, we saw a range of exciting applications for ultra-sensitive molecular detection methods. With increasingly widespread adoption of advanced technologies that continue to drive down the limit of detection for rare mutations, researchers and clinicians are using liquid biopsy and ctDNA analysis to monitor treatment response, quantify resistance mutations, confirm genetic risk factors, and more.

A growing body of oncological data is demonstrating the clinical value of measuring minimal residual disease, sometimes referred to as molecular residual disease, (MRD)—the small number of cancer cells that persist even after a patient is officially in remission following initial treatment. MRD measurement has been long established for predicting relapse and guiding treatment decisions in certain cancers, primarily hematological malignancies such as chronic myeloid leukemia (CML). However, this approach requires standardization in order to be broadly adopted into daily clinical use and maximize patient benefit. Without established standardization, the medical community risks unnecessary variability when interpreting MRD testing results.

Each cancer has a different set of associated biomarkers that can be used to quantify MRD. Some conditions have well defined genetic markers, such as BCR-ABL1 in CML; others demonstrate unique mutational profiles for each patient. Each cancer type or genetic variant will require researchers to establish molecularly quantitative, clinically relevant values for MRD. Once established, researchers can then compare validated MRD assays against other diagnostic and monitoring approaches within clinical trials. These processes and standards will ultimately yield data supporting MRD as a validated, and potentially more sensitive, indicator of treatment efficacy and relapse risk.

To establish usable benchmarks for MRD assays, it is crucial to rely on molecular detection technologies that have extremely high levels of sensitivity and reproducibility. Droplet Digital? PCR (ddPCR?) can achieve rare variant detection sensitivities of <0.1%. It also provides the benefit of absolute quantification of nucleic acids without the need for standards, underpinning its value as a primary reference measurement platform. Given these advantages, ddPCR is an ideal tool for MRD monitoring in research and clinical settings.

With the adoption of advanced, highly sensitive molecular tools like ddPCR technology, we have the opportunity to better define and monitor the mutation profiles of complex diseases like acute myeloid leukemia (AML). Through collaborations like the recently-launched Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium—in which Bio-Rad Laboratories is a proud partner—researchers can leverage the latest technologies and share data to accelerate the validation of biomarkers for MRD testing. With these combined efforts, the goals of better drug trials, streamlined pharmaceutical development, superior treatments, and improved survival rates for cancer patients worldwide become achievable.

To find custom?Droplet Digital PCR?assays for MRD measurements?and other nucleic acid quantification applications, check out Bio-Rad’s?digital PCR assay design engine.